Kidney transplantation is a live-saving therapy for patients with chronic kidney failure. Transplant patients are continuously treated with immunosuppressives that mainly target their adaptive immune system, in order to prevent graft rejection. However, these therapies have severe side effects. Therefore, it is important to develop novel therapeutic strategies. This thesis shows that also the innate immune system, and specifically the development of immunological memory by this system (so-called ‘trained immunity’), plays an important role in graft rejection, and is a predictor of graft survival. T cells were found to modulate the development of trained immunity via the molecule CD40. Short-term suppression of trained immunity induction using nanotherapeutics prolonged graft survival in mice, and long-term graft survival was achieved when combining these nanotherapeutics with a single injection of the medicine CTLA4-Ig. This indicates that short-term suppression of innate immune cells might be a promising therapeutic strategy in organ transplantation.
Maaike Jacobs (1997) obtained her Master's degree in Molecular Mechanisms of Disease cum laude, at the Radboud University in 2020, after which she started her PhD research in the Department of Nephrology of the Radboudumc. In April 2025, she started as clinical chemist in training at Medisch Spectrum Twente in Enschede.